Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance.

Guo Zhang, Hua Bai, Hai Zhang, Camin Dean, Qiang Wu, Juxue Li, Sara Guariglia, Qingyuan Meng, Dongsheng Cai

Neuron 2011 Feb 10

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Hypothalamic neuropeptides play essential roles in regulating energy and body weight balance. Energy imbalance and obesity have been linked to hypothalamic signaling defects in regulating neuropeptide genes; however, it is unknown whether dysregulation of neuropeptide exocytosis could be critically involved. This study discovered that synaptotagmin-4, an atypical modulator of synaptic exocytosis, is expressed most abundantly in oxytocin neurons of the hypothalamus. Synaptotagmin-4 negatively regulates oxytocin exoc ytosis, and dietary obesity is associated with increased vesicle binding of synaptotagmin-4 and thus enhanced negative regulation of oxytocin release. Overexpressing synaptotagmin-4 in hypothalamic oxytocin neurons and centrally antagonizing oxytocin in mice are similarly obesogenic. Synaptotagmin-4 inhibition prevents against dietary obesity by normalizing oxytocin release and energy balance under chronic nutritional excess. In conclusion, the negative regulation of synaptotagmin-4 on oxytocin release represents a hypothalamic basis of neuropeptide exocytosis in controlling obesity and related diseases. Copyright © 2011 Elsevier Inc. All rights reserved.

Citation

Guo Zhang, Hua Bai, Hai Zhang, Camin Dean, Qiang Wu, Juxue Li, Sara Guariglia, Qingyuan Meng, Dongsheng Cai. Neuropeptide exocytosis involving synaptotagmin-4 and oxytocin in hypothalamic programming of body weight and energy balance. Neuron. 2011 Feb 10;69(3):523-35